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Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
06-Nov-2012 - 04-Feb-2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study according to OECD guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
-
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Species: Albino Dunkin Hartley Guinea Pig, HsdPoc: DH, SPF
- Source: Harlan Laboratories B.V., NM Horst / The Netherlands
- Age at study initiation: 4 - 6 weeks
- Weight at study initiation: Intradermal and epidermal pretest: 326.6 - 339 g, control group and test group: 312.9 - 354.8 g
- Housing: In groups of up to ten in stainless steel cages with standard softwood bedding (‘Lignocel’)
- Diet:Teklad Global Guinea pig diet 2040C, ad libitum
- Water: ad libitum
- Acclimation period: 12 days under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3°C
- Humidity (%):
- Air changes (per hr): 10 -15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:
Route:
intradermal and epicutaneous
Vehicle:
paraffin oil
Concentration / amount:
- Intradermal pretest: 50%, 25%, 10% in liquid paraffin
- Epidermal pretest: 100% (undiluted), 50%, 25%, 10% (in liquid paraffin
- Intradermal Induction (Main Test): 10% in liquid paraffin
- Epidermal Induction and challenge (Main test): 100 % (undiluted since the test item was nonirritating based on the results of the range findig pretest)
Route:
epicutaneous, occlusive
Vehicle:
paraffin oil
Concentration / amount:
- Intradermal pretest: 50%, 25%, 10% in liquid paraffin
- Epidermal pretest: 100% (undiluted), 50%, 25%, 10% (in liquid paraffin
- Intradermal Induction (Main Test): 10% in liquid paraffin
- Epidermal Induction and challenge (Main test): 100 % (undiluted since the test item was nonirritating based on the results of the range findig pretest)
No. of animals per dose:
- Intradermal pretest: 1
- Epidermal pretest: 2
- Control group (main test): 5
- Test group (main test): 10
Details on study design:
The intradermal induction of sensitization in the test group was performed in the nuchal region by injection of 10% of the test item in liquid paraffin and an emulsion of Freund's Complete Adjuvant and physiological saline (FCA/0.9% NaCl, 1:1).
One week after the intradermal induction, the epidermal induction of sensitization was performed by topical application of 100% of the test item for
48 hours under occlusion. The skin of the animals had been pretreated with 10% sodium laurylsulfate (SLS) approximately 24 hours prior to
application of the test item.
The animals of the control group were intradermally induced with liquid paraffin and FCA/0.9% NaCl and epidermally induced with liquid paraffin
under occlusion following pretreatment with 10% SLS.
Two weeks after epidermal induction the test and control animals were challenged by epidermal application of 100% test item on the right flank, and no vehicle was applied on the left flank.

- Injection volume (Intradermal injections): 0.1 ml/site
- Volume of formulated or undiluted test item for epidermal applications: 0.2 to 0.3 ml on a filter paper patch;
The animal's fur was shaved with a fine clipper blade just prior to treatment. The filter paper treated with test item, vehicle or 1:1 mixture of
FCA/0.9% NaCl was covered by a strip of aluminium foil and firmly secured by an elastic plaster wrapped around the trunk of the animal and
secured with impervious adhesive tape.
The occlusive dressing was left in place for 24 hours (for the epidermal pretest and epidermal challenge) or 48 hours (for the epidermal induction).
The same patching method was used for the epidermal pretest, the epidermal induction and the epidermal challenge.

Skin reactions were evaluated at 24 and 48 hours after removal of the dressing.
Positive control substance(s):
yes
Remarks:
alpha-hexylcinnamaldehyde (historical data)
Positive control results:
Historical data from an evaluation experiment (Harlan Laboratories Study D65975 Alpha-Hexylcinnamaldehyde)

Based on the above mentioned findings in an adjuvant sensitization test (Guinea PigMaximization test according to Magnusson & Kligman) and in accordance with Regulation (EC) No 1272/2008, alpha-Hexylcinnamaldehyde was confirmed as skin sensitizer as 70% of the test animals responded to the challenge. The sensitivity and reliability of the experimental method was confirmed (see original study: Appendix I - Positive Control).
Reading:
1st reading
Hours after challenge:
24
Group:
other: Control group, not treated (left flank)
Dose level:
not treated
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no clinical signs observerd
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group:
Reading:
1st reading
Hours after challenge:
24
Group:
other: Control group treated with 100% test item (right flank)
Dose level:
undiluted test item
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no clinical signs observed
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: other: Control group treated with 100% test item (right flank). Dose level: undiluted test item. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: no clinical signs observed.
Reading:
1st reading
Hours after challenge:
24
Group:
other: Test group not treated (left flank)
Dose level:
not treated
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no clinical signs observerd
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group:
Reading:
1st reading
Hours after challenge:
24
Group:
other: Test group treated with 100% test item (right flank)
Dose level:
undiluted test item
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no clinical signs observed
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: other: Test group treated with 100% test item (right flank). Dose level: undiluted test item. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no clinical signs observed.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: Control group, not treated (left flank)
Dose level:
not treated
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no clinical signs observed
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group:
Reading:
2nd reading
Hours after challenge:
48
Group:
other: Control group treated with 100% test item (right flank)
Dose level:
undiluted test item
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no clinical signs observed
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: Control group treated with 100% test item (right flank). Dose level: undiluted test item. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: no clinical signs observed.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: Test group, not treated (left flank)
Dose level:
not treated
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no clinical signs observed
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group:
Reading:
2nd reading
Hours after challenge:
48
Group:
other: Test group treated with 100% test item (right flank)
Dose level:
undiluted test item
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no clinical signs observed
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: Test group treated with 100% test item (right flank). Dose level: undiluted test item. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no clinical signs observed.

Summerizing table from original report:

Skin Reactions after the Challenge

After 24 h

Positive/ Total

% Positive of Total

After 48 h

Positive/ Total

% Positive of Total

Control Group

No vehicle

(left flank)

0/5

0/5

0

0

100% test item

(right flank)

0/5

0/5

0

0

Test group

No vehicle

(left flank)

0/5

0/5

0

0

100% test item

(right flank)

0/5

0/5

0

0

Epidermal Induction: No skin reactions were observed in any animal of the test group after epidermal treatment with 100% test item following pre-treatment with 10% SLS in paraffinum perliquidum. No skin reactions were observed in the control group after treatment with the vehicle following pre-treatment with 10% SLS in paraffinum perliquidum.

Challenge: No skin reactions were observed in any of the control (previously not exposed to the test item) and test animals after the challenge with 100% test item.

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the above mentioned findings in an adjuvant sensitization test (Guinea Pig Maximization test according to Magnusson & Kligman) and in
accordance with Regulation (EC) No 1272/2008, Isopropylnaphthalene; Ruetasolv MP has not to be classified as a skin sensitizer.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Skin sensitisation

One valid study is available to assess the skin-sensitising potential of monoisopropylnaphthalene (MIPN, target substance). A study with bis(isopropyl)naphthalene (DIPN, a structure-analogue) served as supporting. In both studies, no sensitising potential has been demonstrated.

Sieber/Harlan 2013

Test results indicate that the test substance MIPN is not sensitising.

Sterner/IBR 1986e

In a valid guinea pig maximization test similar to OECD TG 406, slight erythemas were induced after challenge exposure in the control as well as in test group animals. There was no significant difference between control and test group. Thus, the result obtained with the structure-analogue DIPN provides supportive evidence for the absence of a sensitising potential of MIPB.


Migrated from Short description of key information:
In two studies one using the Guinea Pig Maximisation Test, no indication of a sensitisation potential of monoisopropylnaphthalene (MIPN, target substance) and bis(isopropyl)naphthalene (DIPN, structure-analogue) was observed.

Justification for selection of skin sensitisation endpoint:
No evidence of a sensitising potential in GPMT assays with the target substance.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:
Migrated from Short description of key information:
No information available.
Not required under REACH.

Justification for classification or non-classification

In one valid study with guinea pigs, monoisopropylnaphthalene (MIPN) did not show a skin sensitising potential. According to criteria set in either Directive 67/548/EEC or Regulation (EC) No 1272/2008, MIPN is not sensitising. Classification is not required.